The involvement of nuclear Factor-kappaB (NF-kappaB) transcription factor i
n PC12 cell death triggered by the dopaminergic neurotoxin 6-hydroxydopamin
e (6-OHDA) was investigated. Results show that oxidative stress generated b
y 6-OHDA activates NF-kappaB. When the NF-kappaB activation was inhibited b
y parthenolide, PC12 cell death induced by 6-OHDA was significantly increas
ed, thus suggesting an involvement of this transcription factor in a protec
tive mechanism against 6-OHDA toxicity. To further assess this hypothesis,
we studied the involvement of NF-kappaB in the protective effect of two ant
i-apoptotic genes, bcl-2 and bfl-1. Although Bcl-2 and Bfl-1 expression nor
mally protects PC12 cells from 6-OHDA, parthenolide strongly decreased the
beneficial effects afforded by transgene expression. These results suggest:
(1) that the transcription factor NF-kappaB is likely associated with the
protection of catecholaminergic PC12 cells and (2) that the protective effe
cts afforded by bcl-2 and bfl-1 expression may be dependent on NF-kappaB ac
tivation. (C) 2001 Elsevier Science Inc. All rights reserved.